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Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

Line Kristensen1,2,3, Per Rugaard Poulsen1,3, Eleni Kanouta1,3

  • 1Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.

Frontiers in Oncology
|July 19, 2024
PubMed
Summary

Ultra-high dose rate (FLASH) radiation spares normal tissues within a Spread-out Bragg Peak (SOBP). This study quantified FLASH radiation

Keywords:
FLASH radiationacute toxicitylate toxicitynormal tissue sparingspread-out Bragg peak

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Area of Science:

  • Radiation Oncology
  • Preclinical Research
  • Medical Physics

Background:

  • Ultra-high dose rate (FLASH) radiation shows promise for sparing normal tissues while maintaining tumor control in preclinical studies.
  • Most FLASH research focuses on the beam entrance, but clinical proton therapy utilizes Spread-out Bragg Peaks (SOBP) for targeted dose delivery.
  • Investigating FLASH effects within an SOBP is crucial for clinical relevance.

Purpose of the Study:

  • To quantify the normal tissue-sparing effect of FLASH radiation on acute and late toxicity within a Spread-out Bragg Peak (SOBP).
  • To compare FLASH irradiation to conventional dose rate (CONV) irradiation within an SOBP in a murine model.

Main Methods:

  • Murine hindlegs were irradiated with single-fraction doses using either FLASH (60 Gy/s) or CONV (0.34 Gy/s) dose rates within a 5 cm SOBP.
  • Acute skin toxicity (hair loss, moist desquamation, toe separation) was monitored daily for 29 days.
  • Late toxicity (fibrotic development via leg extendibility) was monitored biweekly for 30 weeks.

Main Results:

  • FLASH irradiation demonstrated significant tissue sparing for acute skin toxicity, with a mean protection ratio of 1.40.
  • Late fibrotic development also showed normal tissue sparing with a protection ratio of 1.18.
  • The observed tissue sparing within the SOBP was comparable to previous findings using entrance-beam irradiations.

Conclusions:

  • FLASH radiation retains its normal tissue-sparing properties when delivered within a Spread-out Bragg Peak (SOBP).
  • A dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development was observed.
  • These findings support the clinical potential of FLASH radiation therapy within SOBPs.